Serotonin, the ‘happy’ neurotransmitter, may not make us so happy


Serotonin is a neurotransmitter located in the brain that is derived from the amino acid tryptophan. Over the years, serotonin has been referred to as the happy neurotransmitter because it is known to have a pivotal role in the reward pathway in the brain, resulting in all those feel-good motions. In fact, drug addiction is so hard to overcome because of the rush of serotonin from the instant activation of the addiction circuit in the human brain.

The first-line pharmacological treatment for depression is a medication class known as selective serotonin reuptake inhibitors (SSRIs), which work by inhibiting the breakdown of serotonin and, as a result, increasing its concentration in the brain. Recently, this happy hormone has raised a lot of controversy with studies stating that it can actually stimulate fear and anxiety in certain regions in the brain.

An overlooked area of the brain

A recent study from the University of North Carolina (UNC) at Chapel Hill discovered that serotonin activates an area in the brain in mice known as the bed nucleus of the stria terminalis (BNST), resulting in anxiety and fear.

“To get to these findings, researchers zapped the paws of the lab mice with electricity and watched a specific area of the brain produce serotonin and deliver it to the BNST. They found that when the flow of serotonin was increased, so were the mouse’s anxiety symptoms. Applying Prozac to the BNST also increased anxiety,” wrote Mike Pearl in an article about the UNC study.

The BNST is a center of integration for the limbic system and is known as the extension of the amygdala due to its role in emotional processing. It has been established that this area plays a role in fear, emotional processing and social awareness.

Two researchers wrote in a recent Molecular Psychiatry article that “the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic-pituitary-adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities.”

A more dynamic action

The amygdala is a small almond-shaped region in the brain that is thought to be responsible for processing fear, but new theories are now questioning this concept and hypothesizing that this region may be responsible for motivation and goal-oriented actions. As humans, many of us are driven by fear, which ties together both of these amygdala theories. Another school of thought regarding this region of the brain is that maybe specific areas do not actually drive a specific emotion such as fear, sadness, surprise and anxiety, but rather each region is more dynamic and many emotions are intertwined within regions of the brain, alluding to more of a gray area.

Is it possible that neurotransmitters such as serotonin can have this dynamic action as well? After all, medical professionals know that SSRIs take an average of four to six weeks to actually work, and in the meantime, patients can become even more depressed than before, increasing the risk of suicide, a black-box warning on all SSRIs. The reason for this is not yet known, but researchers are gaining more knowledge that serotonin may be a double-edged sword – fear and anxiety in some people and happiness in others.

The entire brain is covered in a meshwork of neurotransmitters, including serotonin, and studies have only begun to uncover the tip of the iceberg in terms of which chemicals drive which specific emotions. In fact, emotions are a very small percentage of the role neurotransmitters play, and the very specifics of this intricate science may never be known. Much more research still needs to be developed to have a clearer view of this picture.

About the author

Kristen Fuller, M.D., enjoys writing about evidence-based topics in the cutting-edge world of medicine. She is a physician and author who also teaches, practices medicine in the urgent care setting and contributes to medicine board education. She is also an outdoor and dog enthusiast. 

Leave a Comment

Scroll to Top